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The coronavirus family consists of pathogens that seriously affect human and animal health. They mostly cause respiratory or enteric diseases, which can be severe and life-threatening, such as coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome (SARS), and Middle East Respiratory Syndrome (MERS) in humans. The conserved coronaviral papain-like protease is an attractive antiviral drug target because it is essential for coronaviral replication, and it also inhibits host innate immune responses. This review focuses on the